title: Chronic inflammation and oxidative stress: the smoking gun for Helicobacter pylori-induced gastric cancer?
abstract: Helicobacter pylori is the leading risk factor associated with gastric carcinogenesis. H. pylori leads to chronic inflammation because of the failure of the host to eradicate the infection. Chronic inflammation leads to oxidative stress, deriving from immune cells and from within gastric epithelial cells. This is a main contributor to DNA damage, apoptosis and neoplastic transformation. Both pathogen and host factors directly contribute to oxidative stress, including H. pylori virulence factors, and pathways involving DNA damage and repair, polyamine synthesis and metabolism, and oxidative stress response. Our laboratory has recently uncovered a mechanism by which polyamine oxidation by spermine oxidase causes H 2O 2 release, DNA damage and apoptosis. Our studies indicate novel targets for therapeutic intervention and risk assessment in H. pylori-induced gastric cancer. More studies addressing the many potential contributors to oxidative stress, chronic inflammation, and gastric carcinogenesis are essential for development of therapeutics and identification of gastric cancer biomarkers.
authors.affiliation: Department of Pathology, Microbiology and Immunology; Vanderbilt University Medical Center; Nashville, TN USA; Division of Gastroenterology, Hepatology and Nutrition; Department of Medicine; Vanderbilt University Medical Center; Nashville, TN USA.
authors.forename: Dana M
authors.initials: DM
authors.lastname: Hardbower
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition; Department of Medicine; Vanderbilt University Medical Center; Nashville, TN USA.
authors.forename: Thibaut
authors.initials: T
authors.lastname: de Sablet
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition; Department of Medicine; Vanderbilt University Medical Center; Nashville, TN USA.
authors.forename: Rupesh
authors.initials: R
authors.lastname: Chaturvedi
authors.affiliation: Department of Pathology, Microbiology and Immunology; Vanderbilt University Medical Center; Nashville, TN USA; Division of Gastroenterology, Hepatology and Nutrition; Department of Medicine; Vanderbilt University Medical Center; Nashville, TN USA; Veterans Affairs Tennessee Valley Healthcare System; Nashville, TN USA; Department of Cancer Biology; Vanderbilt University Medical Center; Nashville, TN USA.
authors.forename: Keith T
authors.initials: KT
authors.lastname: Wilson
mesh_terms: D017209:Apoptosis; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D002908:Chronic Disease; D004249:DNA Damage; D004847:Epithelial Cells / Q000378:metabolism; D016481:Helicobacter Infections / Q000150:complications / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000382:microbiology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism; D013274:Stomach Neoplasms / Q000209:etiology / Q000382:microbiology*; D000097667:Polyamine Oxidase
chemical_list: D006861:Hydrogen Peroxide; D000587:Oxidoreductases Acting on CH-NH Group Donors; D000097667:Polyamine Oxidase
keywords: 8-oxoguanosine; DNA damage; Helicobacter pylori; gastric carcinogenesis; oxidative stress; spermine oxidase; stomach